The purpose of this application is to investigate the pathogenesis and pathophysiology of exercise-induced asthma (EIA). To achieve these goals, we propose to: (1) determine if nitric oxide (NO) excretion is thermally sensitive; (2) Explore the source of NO; and (3) examine the role of vascular-permeability in EIA and its dependence upon NO and the leukotrienes. The first set of experiments will test the hypothesis that NO is generated by the airway epithelium as a function of the local temperature changes that develop during hyperpnea in order to regulatory respiratory heat exchange. It also seeks to determine if EIA is an exaggerated response to normal physiologic events or whether it derives from a combination of over production of mediators superimposed upon abnormal airway components. The second set explores the relative contribution of epithelial and vascular sources of NO in the exhaled air obstruction. The final experiments focus upon the physiologic events that lead to bronchial obstruction and test the premise that the airway narrowing in EIA derives from increased capillary permeability and that NO and the leukotrienes are involved in the process.